Introduction: The BK polyomavirus (BKPyV) remains latent in immunocompetent individuals but can reactivate in patients who are immunosuppressed, such as kidney transplant recipients (KTR). This reactivation can lead to viral shedding into the bloodstream, causing BK nephropathy, potentially resulting in impaired graft function or graft loss. Currently, there is no established antiviral treatment for BKPyV. Guidelines recommend reducing immunosuppressive therapy, but this can result in difficult to treat acute rejection. Adjunctive treatments such as intravenous immunoglobulin (IVIG), known for its potential antiviral and immunomodulatory properties, and cidofovir, which has demonstrated in-vitro efficacy against polyomaviruses, are being explored. This study seeks to evaluate the effectiveness of IVIG and/or cidofovir combined with immunosuppression (IS) reduction in comparison to IS reduction alone in pediatric KTR.
Methods: This was a single-center, retrospective chart review of 150 pediatric KTR between January 2010 and December 2023. KTR who were found to have greater than 500 copies/mL of BKPyV in plasma were included in the study. Data collected includes patient demographics, time to first occurrence of undetected BKPyV in plasma, serum creatinine, biopsy proven acute rejection, BK nephropathy, and development of donor specific antibodies.  In those with BKPyV, IS was reduced in a step-wise manner:  Initially, MMF was decreased by 50% then discontinued, followed by reduction in target tacrolimus levels of 3-5 ng/mL. If KTR demonstrated persistent high-level viremia or evidence of graft dysfunction, IVIG (1gm/kg) was given monthly and/or Cidofovir 0.25-0.5 mg/kg/dose administered weekly. 
Results: A total of 32 KTR (~20%) were found to have BKPyV in plasma during the study period. The median age was 7.6 years (IQR 10) with 13 males (41%) and 18 (58%) of Hispanic ethnicity. Of the 32 KTR, 15 (45%) were managed with reduction in IS alone (Group 1). KTR that received adjunctive therapy tended to develop BKPyV later post-transplant (Group 2) compared with Group 1 KTR (372 IQR 384 vs 217 IQR 717 days). For every one day increase in time of transplant to detection in the plasma, there was a 0.4% (p = 0.7) increase in the time to not detected in the plasma. When taking into consideration the time Group 2 started treatment, there was an 68.4% (p = 0.44) decrease in time to resolution of BK viremia in Group 2 compared with Group 1. Biopsies were more likely to demonstrate acute and chronic rejection Group 2: 31% vs Group 1: 0% (p = 0.29).  There was no significant difference between highest viral load and time to resolution. 
Conclusions: In addition to IS reduction, adjunctive therapy with cidofovir and IVIG demonstrated a trend toward earlier resolution of BK viremia. These therapies may have clinical benefit in KTR with more severe disease and could prevent graft loss. Prospective and controlled trials are needed to confirm efficacy.